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2020-03-06

AstraZeneca: Update on Phase III DANUBE trial for Imfinzi and tremelimumab in unresectable, Stage IV bladder cancer

The Phase III DANUBE trial for Imfinzi (durvalumab) and Imfinzi plus
tremelimumab in unresectable, Stage IV (metastatic) bladder cancer
did not meet the primary endpoints of improving overall survival (OS)
versus standard-of-care (SoC) chemotherapy for Imfinzi monotherapy in
patients whose tumour cells and/or tumour-infiltrating immune cells
express high levels (?25%) of PD-L1, or for Imfinzi plus tremelimumab
in patients regardless of their PD-L1 expression.

José Baselga, Executive Vice President, Oncology R&D, said:
"AstraZeneca remains committed to addressing unmet needs in bladder
cancer and the potential for immunotherapy to improve outcomes for
these patients. The results from this trial will inform our
comprehensive Phase III development programme in bladder cancer. We
look forward to the results of the Phase III NILE trial also in the
1st-line metastatic setting, and we continue to advance clinical
trials for patients at earlier stages of the disease."

The safety and tolerability profiles for Imfinzi and the combination
with tremelimumab were consistent with previous trials. The data will
be presented at a forthcoming medical meeting.

Imfinzi is being developed in patients with unresectable, locally
advanced or metastatic bladder cancer in the Phase III NILE trial
either in combination with chemotherapy or with chemotherapy and
tremelimumab. Imfinzi is also being tested in earlier stages of
bladder cancer in the Phase III NIAGARA trial in combination with
chemotherapy, and in the Phase III POTOMAC trial in combination with
SoC Bacillus Calmette-Guerin immunotherapy.

Imfinzi is approved for patients with locally advanced or metastatic
bladder cancer previously treated with platinum-containing
chemotherapy in 15 countries, including the US.

Bladder cancer

In 2018, approximately 550,000 people were diagnosed with bladder
cancer around the world and 200,000 died from the disease.[1] Locally
advanced and metastatic bladder cancer remains an area of unmet
medical need and typically only one in seven patients are alive five
years after diagnosis.[2] Urothelial cancer (UC) is the most common
form of bladder cancer.[3] UC is the 10th most common cancer
worldwide and the 13th most common cause of cancer death.[1,4] PD-L1
is widely expressed in tumour and immune cells in patients with
bladder cancer and helps tumours evade detection from the immune
system.[5]

DANUBE

DANUBE is a randomised, open-label, multi-centre, global, Phase III
trial in the 1st-line treatment of both cisplatin eligible and
ineligible patients with unresectable, Stage IV (metastatic) UC. The
trial compared Imfinzi monotherapy or Imfinzi plus tremelimumab
versus cisplatin and gemcitabine or carboplatin and gemcitabine
chemotherapy. The trial was conducted in more than 220 centres across
24 countries, including centres in the US, Canada, Europe, South
America, Asia, Australia and the Middle East.

Eligible patients included those with transitional cell carcinoma of
the urothelium, including renal pelvis, ureters, urinary bladder, and
urethra. High PD-L1 was defined as ?25% of tumour cells (TC) or
tumour-infiltrating immune cells (IC) expressing membrane PD-L1 if
ICs involved >1% of the tumour area, or TC?25% or IC=100% if ICs
involved ?1% of the tumour area.

The primary endpoints of the trial were OS in high PD-L1 patients
treated with Imfinzi monotherapy, and OS in patients treated with
Imfinzi plus tremelimumab regardless of their PD-L1 status. The
DANUBE trial addresses a post-approval commitment in agreement with
the US Food and Drug Administration from the May 2017 accelerated US
approval of Imfinzi in previously treated patients with advanced
bladder cancer.

Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to
PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80,
countering the tumour's immune-evading tactics and releasing the
inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable,
Stage III non-small cell lung cancer (NSCLC) after chemoradiation
therapy in 61 countries, including the US, Japan, China and across
the EU, based on the Phase III PACIFIC trial. Imfinzi recently
received its first global approval for the 1st-line treatment of
extensive-stage small cell lung cancer (ES-SCLC) in combination with
SoC chemotherapy in Singapore.

As part of a broad development programme, Imfinzi is also being tested
as a monotherapy and in combinations including with tremelimumab, an
anti-CTLA4 monoclonal antibody and potential new medicine, as a
treatment for patients with NSCLC, SCLC, bladder cancer, head and
neck cancer, liver cancer, biliary tract cancer, cervical cancer and
other solid tumours.

Tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicine
that targets the activity of cytotoxic T-lymphocyte-associated
protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4,
contributing to T cell activation, priming the immune response to
cancer and fostering cancer cell death. Tremelimumab is being tested
in a clinical trial programme in combination with Imfinzi in NSCLC,
SCLC, bladder cancer, head and neck cancer and liver cancer.

AstraZeneca's approach to Immuno-Oncology (IO)

Immuno-oncology (IO) is a therapeutic approach designed to stimulate
the body's immune system to attack tumours. The Company's IO
portfolio is anchored by immunotherapies that have been designed to
overcome anti-tumour immune suppression. AstraZeneca believes that
IO-based therapies offer the potential for life-changing cancer
treatments for the clear majority of patients.

The Company is pursuing a comprehensive clinical-trial programme that
includes Imfinzi as a monotherapy and in combination with
tremelimumab in multiple tumour types, stages of disease, and lines
of therapy, and where relevant using the PD-L1 biomarker as a
decision-making tool to define the best potential treatment path for
a patient. In addition, the ability to combine the IO portfolio with
radiation, chemotherapy, small targeted molecules from across
AstraZeneca's Oncology pipeline, and from research partners, may
provide new treatment options across a broad range of tumours.

AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential to
transform patients' lives and the Company's future. With six new
medicines launched between 2014 and 2020, and a broad pipeline of
small molecules and biologics in development, the Company is
committed to advance oncology as a key growth driver for AstraZeneca
focused on lung, ovarian, breast and blood cancers. In addition to
AstraZeneca's main capabilities, the Company is actively pursuing
innovative partnerships and investments that accelerate the delivery
of our strategy, as illustrated by the investment in Acerta Pharma in
haematology.

By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development of
personalised combinations, AstraZeneca has the vision to redefine
cancer treatment and one day eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery, development
and commercialisation of prescription medicines, primarily for the
treatment of diseases in three therapy areas - Oncology,
Cardiovascular, Renal and Metabolism, and Respiratory. Based in
Cambridge, UK, AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow
the Company on Twitter @AstraZeneca
(https://twitter.com/AstraZeneca).

Media Relations
Gonzalo Viña +44 203 749 5916
Rob Skelding Oncology +44 203 749 5821
Rebecca Einhorn Oncology +1 301 518 4122
Matt Kent BioPharmaceuticals +44 203 749 5906
Angela Fiorin BioPharmaceuticals +44 1223 344 690
Jennifer Hursit Other +44 203 749 5762
Christina Sweden +46 8 552 53 106
Malmberg
Hägerstrand
Michele Meixell US +1 302 885 2677
Investor
Relations
Thomas Kudsk +44 203 749 5712
Larsen
Henry Wheeler Oncology +44 203 749 5797
Christer BioPharmaceuticals +44 203 749 5711
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Nick Stone BioPharmaceuticals (Renal) +44 203 749 5716
Environmental, Social and
Governance
Josie Afolabi BioPharmaceuticals +44 203 749 5631
(Respiratory)
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Kretzmann investors
US toll-free +1 866 381 72 77

References

1. World Health Organization International Agency for Research on
Cancer. Cancer Fact Sheets - Bladder. Available at
http://gco.iarc.fr/today/data/factsheets/cancers/30-Bladder-fact-sheet.pdf
Accessed February 2020.

2. Von der Maase H, et al. Long-Term Survival Results of a Randomized
Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate,
Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder
Cancer. J Clin Oncol. 2005;23:4602-4608.

3. American Society of Clinical Oncology. Bladder Cancer:
Introduction. Available at
https://www.cancer.net/cancer-types/bladder-cancer/introduction.
Accessed February 2020.

4. World Cancer Research Fund. Bladder cancer statistics. Available
at
https://www.wcrf.org/dietandcancer/cancer-trends/bladder-cancer-statistics.
Accessed February 2020.

5. Magdalene J, et al. Joseph M, et al. Immune Responses in Bladder
Cancer-Role of Immune Cell Populations, Prognostic Factors and
Therapeutic Implications. Front Oncol.2019;9:1270.

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